The present invention relates to the therapeutic treatment of systemic bacterial infections in non-human mammals by the oral administration on a once a day basis of ormetoprim-potentiated sulfonamides.
Modern methods of raising groups of farm animals and companion animals in confined areas enhance the incidence of microbial respiratory infection and other types of systemic infectious diseases. Such incidences vary from sporadic to enzootic, and the course of infection varies from acute to subacute to chronic. The outcome of the infection may be an uneventful recovery, but frequently severe weight loss, chronic disease conditions or death due to pathological changes in the animals may occur. Bacteria such as Hemophilus, Bordetella, Pasteurella, Staphylococcus, Salmonella, Klebsiella, Actinobacillus, Clostridium and other aerobic and anaerobic genera are usually isolated from clinical cases, implicating them in the causation of respiratory and other systemic diseases.
The health of farm and other animals can to an extent be regulated by the use of chemical and biological agents, which are injected into the animal or administered orally, for example, directly as a bolus or by addition to the feed or drinking water. Such agents include chemotherapeutic drugs for treating or preventing bacterial infections in animals and growth promoting additives for inclusion in livestock feed.
Diaminopyrimidine-potentiated sulfonamides are known to be useful as therapeutic or prophylactic agents in the control of diseases in animals. Such drugs are utilizable in turkey feed to prevent fowl cholera; see, for instance, Siegel et al., Avian Diseases, Volume 23, pages 409-416 (1979), and Olson, Poultry Science, Volume 56, pages 1098-1101 (1977). They are useful to treat coccidiosis, a parasitic infection in chickens; Orton et al., Poultry Science, Volume 50, pages 1341-1346 (1971). They have been studied as chemotherapeutic agents against Salmonella, Escherichia and Pasteurella in poultry; Mitrovic et al., Poultry Science, Volume 57, p. 1159 (1978), Olesiuk et al., Avian Diseases, Volume 17, pages 379-389 (1973); Sandhu et al., Poultry Science, Volume 59, pages 1027-1030 (1980). See also Havas et al., Chemotherapy, Volume 19, pages 179-195 (1973). It has also been revealed that the combination of sulfadimethoxine and ormetoprim is effective in pigs against localized digestive tract infections caused by Escherichia coli, Proceedings International Pig Vet. Soc., 1980 Congress, Copenhagen, Denmark; as well as Sphaerophorus necrophorus--induced experimental infections in mice, Maestrone et al., The Cornell Veterinarian, Volume 65, No. 2, pages 187-204 (1975). See also U.S. Pat. No. 3,461,206 to Hoffer et al. which disclose compositions of 2,4-diamino-5-(2',4',5-trisubstituted benzyl)pyrimidines and a sulfonamide as anticoccidial and antibacterial agents for poultry.
Diaminopyrimidine-potentiated sulfonamides have also been studied as chemotherapeutic agents against bacterial infections in horses; see, for instance, Adamson et al., Am. J. Vet. Res., Volume 46, pages 447-450 (1985); Brown et al., Am. J. Vet. Res., Volume 49, pages 918-922 (1988); and Brown et al., Am. J. Vet. Res., Volume 53, pages 12-16 (1989). Diaminopyrimidine-potentiated sulfonamides have also been studied as anticoccidiostats in dogs and coyotes. Dunbar et al., Am. J. Vet. Res., Volume 46, pages 1899-1902 (1985).
Injectable formulations of diaminopyrimidine-potentiated sulfonamides have been disclosed for the therapeutic treatment of bacterial infections in birds and mammals other than humans; U.S. Pat. No. 3,551,564 (Klaui et al.), U.S. Pat. No. 3,728,452 (Haber et al.), and U.S. Pat. No. 4,031,214 (Easterbrook et al.).
In addition, it has been established that potentiated sulfonamides promote growth in healthy farm animals, such as hogs, when added to the feed or drinking water; U.S. Pat. No. 3,715,433 (Bauernfeind et al).